tbuckley/cabot-search huggingface dataset:
A systematic review of Merkel cell carcinoma epidemiology highlights its rising incidence, poor prognosis and data heterogeneity
Authors: Khaylen Mistry, Zoe C Venables
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof A systematic review of Merkel cell carcinoma epidemiology highlights its rising incidence, poor prognosis and data heterogeneity Get access Khaylen Mistry, Khaylen Mistry Conceptualization, Validation, Writing - original draft, Writing - review & editing Department of Dermatology, Norfolk and Norwich University HospitalNorwich Medical School, University of East Anglia, Norwich, UK Correspondence: Khaylen Mistry. Email: khaylen.mistry@nnuh.nhs.uk https://orcid.org/0000-0003-4770-9335 Search for other works by this author on: Oxford Academic Google Scholar Zoe C Venables Zoe C Venables Conceptualization, Validation, Writing - review & editing Department of Dermatology, Norfolk and Norwich University HospitalNorwich Medical School, University of East Anglia, Norwich, UK https://orcid.org/0000-0002-9929-2693 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad434, https://doi.org/10.1093/bjd/ljad434 Published: 09 November 2023 Article history Received: 24 October 2023 Accepted: 29 October 2023 Published: 09 November 2023 Corrected and typeset: 29 November 2023
IMMU-16. PUBLIC TUMOR-WIDE NEOANTIGENS DERIVED FROM CLONAL ABERRANT SPLICING EVENTS DRIVE TUMOR-SPECIFIC T-CELL RESPONSES
Authors: Darwin Kwok, Nicholas Stevers, Takahide Nejo, Jangham Jung, Lee Chen, Senthilnath Lakshmanachetty, Inaki Etxeberria, Marco Gallus, Akane Yamamichi, Emilio Ramos, Chibo Hong, Maggie Colton, Gary Chan, Aidan Du, James Woo, Arun Wiita, Christopher Klebanoff, Joseph Costello, Hideho Okada
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Immunotherapy in gliomas is limited by tumor heterogeneity and low mutational burden. We developed a novel comprehensive in silico pipeline for detecting tumor-specific splicing events (neojunctions) across multiple cancer types, and in gliomas, we successfully identified tumor-wide, public, alternatively spliced neoantigens (ASNs) that elicit CD8+ T-cell-mediated immune responses. METHODS Our pipeline identified recurring public neojunctions expressed in TCGA RNA-seq (positive sample rate (PSR) &amp;gt; 10%) and not in GTEx normal tissue RNA-seq data (PSR &amp;lt; 1%) across six cancer types. To characterize intratumorally-conserved neojunctions, we utilized multi-site RNA sequencing, and with gliomas, we analyzed approximately 10 maximally-distanced intratumoral sites within 56 patients (n=535). Tumor-wide public neojunction expression was subsequently validated in RNA-sequencing and mass spectrometry (MS) data from patient-derived cell lines (n=68) and samples (n=99). Two independent algorithms then predicted peptide processing likelihood and HLA-binding affinity of ASN candidates. In vitro sensitization (IVS) of healthy donor-derived CD8+ T-cells against high-confidence ASN candidates, followed by 10x VDJ scRNA-seq, was performed to identify ASN-specific TCR sequences. TCRs were transduced into triple-reporter Jurkat76s and co-cultured with ASN and HLA-expressing COS7 cells and glioma cell lines to evaluate TCR functionality. RESULTS Our glioma-specific analysis identified 249 public neojunctions with varying intratumoral heterogeneity. 4 ASNs were concurrently identified in transcriptomic and proteomic glioma data and predicted to be presented by HLA-A*02:01 with high confidence. IVS and subsequent 10x VDJ scRNA-seq on expanded CD8+ populations identified TCR clonotypes reactive against neojunctions in RPL22 (n=7) and GNAS (n=1), the latter being highly intratumorally-conserved (detected in &amp;gt; 90% of spatially-mapped biopsies across 17/56 patients (26.78%)). TCR-transduced T-cells demonstrated recognition and immunogenic activation against endogenously processed and presented neoantigens in glioma and transfected COS7 cells. CONCLUSION Our unique integrative pipeline identified novel public tumor-wide splice-derived neoantigen candidates and TCRs, offering a promising off-the-shelf immunotherapy approach for gliomas.
QOL-20. INCLUDING BRAIN METASTASES PATIENTS IN PSYCHOLOGICAL INTERVENTIONS: A PHASE II SINGLE-ARM INVESTIGATION OF MANAGING CANCER AND LIVING MEANINGFULLY
Authors: Ashlee Loughan, Autumn Lanoye, Alexandria Davies, Kelcie Willis, Sarah Braun, Chris Kleva, Amber Fox, Giuliana Zarrella, Gary Rodin
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Patients with brain cancer demonstrate substantial psychological distress yet are frequently excluded from psychological research. Managing Cancer and Living Meaningfully (CALM), an expressive-supportive psychotherapy designed to address the challenges faced by patients with advanced cancer. CALM is proven to reduce depression and death-related distress; however, patients with brain metastases (bMETs) have not been formally examined for CALM’s appropriateness or effectiveness. METHODS In this ongoing Phase II trial, 15 adults with bMETs and heightened distress (PHQ/DADDS) participate in a six-session CALM intervention and complete intervention satisfaction surveys and interviews. Data collection includes established feasibility and acceptability metrics, intervention satisfaction surveys and interviews, and changes in distress patient reported outcomes (pre-to-post CALM). RESULTS Of 21 patients screened, 15 enrolled in the study (73% female; 80% White; Mage = 58yrs). All 15 bMET participants completed baseline assessments, with 13 trial initiators, and 2 screen fails. To date, 8 participants have completed treatment. Reasons for withdrawal include disinterest in intervention topics (n = 1) and lost to follow-up (n = 2). Retention is 73%, with 2 participants still in active treatment. No adverse events were determined to be study-related. Perceived benefit was high (4.3/5), and all participants reported they would recommend the program to others. Reductions in depression severity were demonstrated in 6 of 8 completed participants (MPHQ Reduction = 7.6, range = 2-11) and in death anxiety severity for 7 of 8 completed participants (MDADDS-F1 Reduction = 14.7, range = 6-23). CONCLUSIONS Preliminary data suggests that CALM is both feasible and acceptable among adult patients with bMETs. Enrollment and retention rates are adequate. Patients report high benefit and recommendation to others. Overall, depression and death-related distress severity scores improved, suggesting CALM may be a promising intervention for neuro-oncology patients as they navigate the challenges of metastatic brain cancer. These findings support advancement to the next stage, a Phase II pilot RCT.
NCOG-25. SINGLE-INSTITUTION SERIES OF SPINAL EPENDYMOMA IN CHILDREN WITH NF2-RELATED SCHWANNOMATOSIS
Authors: Noah Burket, Jenna Koenig, Jignesh Tailor
Journal: Neuro-Oncology (2023)

Abstract NF2-related schwannomatosis (NrS) is a tumor predisposition syndrome that results in the development of multiple central nervous system tumors, including spinal ependymomas (SP-EPN). SP-EPN are intramedullary tumors that are slow growing but can displace critical nerve pathways in the spinal cord, resulting in motor and sensory deficits that contribute to patient morbidity. Although surgery is the mainstay of treatment, it can also result in high morbidity, resection of sporadic SP-EPN is often curative; however, SP-EPN in NrS patients will often regrow, possibly resulting in additional surgeries and a lifetime of deficits, especially impacting pediatric patients. Yet, natural history and clinical outcomes for pediatric NrS patients with SP-EPN have not been well described. We reviewed 27 pediatric NrS patient cases from 1993 to 2023 at our institution and identified 10 patients with a diagnosis of SP-EPN, with a range of 1-3 tumors present at patient diagnosis. Demographic, clinical, pathologic, and radiologic data were collected from electronic medical records. Median age of diagnosis of NrS was 12 years old (range: 5-17) and median time from NrS diagnosis to SP-EPN diagnosis was 31 days (range: -1-1636). 14 out of 16 (87.5%) initial tumors were in the cervical spine region, with C2 being the most frequently involved level. Two patients underwent resection of their tumors, with both experiencing progression of their disease and one developing paraplegia. The most common symptoms from SP-EPN were pain (30%), motor deficits (30%), and sensory deficits (30%). 40% of the patients had progressive disease at last follow up, with median time from diagnosis to progression of 3.33 years. Median time from SP-EPN to last follow-up was 4.08 years. This series showcases the burden of SP-EPN in pediatric NrS patients, emphasizing the need for further exploration into clinical outcomes and novel treatments for this debilitating condition.
QOL-04. CHANGES IN FUNCTIONAL CONNECTIVITY AFTER SURGERY ARE ASSOCIATED WITH DECLINE IN FUNCTIONAL INDEPENDENCE IN PATIENTS WITH ELOQUENT GLIOMA
Authors: Kyle Noll, Mariana Bradshaw, Henry Chen, Jeffrey Wefel, Catherine Sullaway, Ashley Thomas, Vinodh Kumar, Sujit Prabhu, Ho-Ling Liu
Journal: Neuro-Oncology (2023)

Abstract It is unknown whether patient independence following resection of eloquent glioma is associated with postoperative functional connectomic changes. Fifteen patients with left perisylvian glioma underwent resting-state fMRI and neuropsychological evaluation before and about 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Manual dexterity testing (Grooved Pegboard; N = 13), neurologic motor exam (N = 12), and performance status (KPS; N = 14) were also obtained. Graph theoretical analysis was used to calculate functional brain network properties. Postoperative need for assistance in at least 1 activity on the IADL increased from baseline in 80% of patients, most commonly in Transportation (67%), followed by Shopping (60%), Financial Management (47%), Cooking (47%), Medication Management (33%), and Phone Use (33%). Overall need for assistance (Total IADL score) significantly increased postoperatively (Mdn change = 4, p = .006). Need for assistance on the PSMS only increased in 27% of patients, with rates less than 15% across all functions. Total PSMS scores did not differ pre- and postoperatively (Mdn change = 0). KPS scores worsened in 40% of patients. None had gross motor worsening, though fine manual dexterity declined in 7% for the left and 23% for the right hand. Increased connectomic properties were significantly associated (Spearman ρ) with greater need for assistance on the IADL [Local Efficiency: Total (.72), Shopping (.71), Cooking (.64), Financial Management (.64); Clustering Coefficient: Phone Use (.63); Betweenness Centrality: Phone Use (.63); all p &amp;lt; .01]. PSMS and IADL ratings were not associated with KPS, manual dexterity, pre/postoperative FLAIR volume, or extent of resection. This study demonstrated that increases in certain functional connectomic properties after surgery are associated with greater need for assistance in instrumental activities in the postoperative period. Connectivity increases have also been associated with poorer cognitive outcome in this population, though specific properties involved may differ.
QLTI-08. THE COLUMBIA NEURO-ONCOLOGY RESEARCH DASHBOARD: A WEB-BASED TOOL TO ASSESS CLINICAL TRIAL RECRUITMENT AND ACCRUAL METRICS
Authors: Mary Welch, Peter Pan, Aya Haggiagi, Laura Donovan, Maria Diaz, Fabio Iwamoto, Andrew Lassman
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Insufficient trial participation is a recognized barrier to drug development. Research has focused on patient and physician-associated factors, yet few institutions assess the impact of trial availability, referral patterns, and patient eligibility. Screening logs provide a rough estimate of candidate pools but tell us nothing about patients who are not screened, let alone why. To better understand site-specific barriers and effectively assess efforts to overcome them, real-time, data-driven metrics are essential. METHODS To address this need, we created The Columbia Neuro-Oncology Clinical Research Dashboard (CRD), a web-based tool designed to capture all patients presenting to our faculty practice with newly diagnosed or recurrent CNS tumors and track their participation -- or lack thereof -- in interventional trials. From 7/2022 - 9/2022, we experimented with several iterations of the CRD, adjusting the platform and variables in response to user feedback. To pilot the final design, we started with a limited sample of high-grade glioma patients seen at Columbia University Irving Medical Center's Neuro-Oncology Faculty Practice from 9/1/2022 - 1/1/2023. During this period, 62 patients were tracked, allowing for further refinements to improve functionality and data capture. When populated, the CRD was easily queried for important quality improvement metrics including accrual rates, time from presentation to study initiation and grounds for screen failure. It also captured the percentage of patients who were not offered a trial and the cited reasons. Inclusion of demographics and referral patterns provided additional dimensions to the data. NEXT STEPS: The CRD has met its preliminary aims. It provides a user friendly and accessible interface for data capture. With appropriate staffing and implementation processes in place, it has real potential to inform our efforts to improve patient accrual and diversity with real-time metrics. Subsequent efforts will focus on these aspects of the project.
RADT-39. CYBERKNIFE: THE CURRENT STATE OF LINAC AS TREATMENT FOR VESTIBULAR SCHWANNOMAS
Authors: Nolan Brown, Basel Musmar, Oanh Nguyen, Zachery Neil, Cathleen Kuo, Julian Gendreau
Journal: Neuro-Oncology (2023)

Abstract INTRODUCTION In the present study, we systematically review the extant literature describing CyberKnife radiosurgery (CKRS) as treatment for vestibular schwannoma (VS). We then perform pooled meta-analysis of long-term tumor control and hearing preservation rates reported across all retrospective observational series describing the efficacy of CKRS. METHODS We queried three databases to identify all primary retrospective studies reporting local tumor control and hearing preservation rates following CKRS for treatment of vestibular schwannoma. All studies returned across the three databases were subject to systematic screen according to pre-defined inclusion and exclusion criteria in a multi-step process performed by two investigators. RESULTS Following a comprehensive systematic search, a total of 15 studies comprising 2018 vestibular schwannoma patients were included. The proportion of females ranged from 30% to 60.3%, and the mean age of all 2,018 patients was 60.2 years. There were 64 patients who had neurofibromatosis type 2 (NF-2). Additionally, 309 patients had previously undergone surgical resection and/or radiosurgery for VS. In regard to CKRS treatment parameters, the marginal dose ranged from 1.9-25.78 Gy. The mean follow-up duration across the included studies was 40.0 months. Pooled rate of tumor control using the random effects model was 96% (95% CI: 95%-98%), and that of hearing preservation was 73% (95% CI: 66%-81%). The most common major complications following CKRS were trigeminal neuralgia, facial neuropathy, and hydrocephalus. CONCLUSIONS As studies on CyberKnife radiosurgery, one of the SRS modalities administered via LINAC, are far less common than studies on Gamma Knife radiosurgery for treatment of VS, more studies are needed in order to solidify the findings reported in the present meta-analysis. Although there are currently only 15 single-institution retrospective studies available in the neurosurgical literature, this study provides the most comprehensive and up-to-date analysis of highly relevant outcomes of interest in treatment of vestibular schwannoma via CyberKnife.
QOL-07. RESISTING DECLINES IN FUNCTIONAL FITNESS: PRELIMINARY FINDINGS FROM THE RESIST TRIAL
Authors: Melanie Keats, Chris Blanchard, Jonathon Fowles, Scott Grandy, Jodi Langley, Alex LeBlanc, Heather Neyedli, Adrienne Weeks, Mary MacNeil
Journal: Neuro-Oncology (2023)

Abstract Few studies have evaluated the efficacy of exercise (EX) in mitigating the functional decline experienced by glioblastoma patients receiving steroids. Here we report preliminary findings on the impact of a tailored ~12-week circuit-based resistance training (CRT) program on functional fitness in glioblastoma patients on treatment. Patient accrual, adherence, and safety was evaluated throughout. Functional status (Short Physical Performance Battery) and grip strength were assessed at baseline and post-study. Depending on the treatment protocol, EX participants completed 3-6 weeks of in-person training followed by 6-9 weeks of home-based, Zoom facilitated training (3-4, 25–30-minute sessions/week). From March 2022 to May 2023, 33 glioblastoma patients were screened and met eligibility criteria, 24 expressed interest, and 15 subsequently agreed to participate (45% accrual). Participants were randomly allocated to either the EX (n = 7) or wait-list control (CON = 8) group. Ten participants (EX = 5; CON = 5) have completed the study with 1 CON ongoing (27% attrition; 2 withdrawn; 2 died) and incomplete fitness data for 1 EX participant. Three serious, unrelated adverse events were recorded, including 2 disease related deaths and 1 hospitalization. Adherence to in-person EX sessions was 96%. While not significant, preliminary efficacy data suggests that EX participants were more likely to maintain or mitigate losses in lower body function (CON (Mchange=-1.0, SD = 2.6); EX (Mchange = 0; SD = 1.3), t(7)=0.943, p &amp;gt; 0.05, d = 0.49) and grip strength (CON (Mchange=-5.94kg, SD = 9.15; EX (Mchange = 0.4kg, SD = 5.75), t(7)=0.269, p &amp;gt; 0.05, d = 0.83). Findings show that glioblastoma patients on active treatment are willing and able to safely engage in CRT. Participants were adherent to in-person CRT sessions, however self-reported home-based CRT was low, with many participants disengaging from EX. While this may be attributed to declining health and worsening fatigue related to ongoing treatments, additional study is needed to explore strategies to improve adherence to home-based EX sessions as in-person sessions are not always feasible.
SURG-05. HYPER SMART CYBER OPERATING THEATER TO PERFORM FUTURE PREDICTIVE SURGERY
Authors: Yoshihiro Muragaki, Ken Masamune, Takashi Sasayama, Takakazu Kawamata
Journal: Neuro-Oncology (2023)

Abstract Gliomas are invasive tumors in which the extent of tumor resection is believed to correlate with prognosis. However, aggressive extraction risks deterioration due to functional tissue damage. One strategy for resolving this conflict is the technology of new modalities. The basis of this technology is digital transformation (DX), converting analog information called tacit knowledge on experiences into digital information for explicit knowledge. In the future, we will develop an AI system, generated by DX data, and support intraoperative decision-making with highly accurate future predictions. In order to realize this future-prediction surgery, we have developed a smart cyber operating theater (SCOT) with intraoperative MRI. More than 20 medical devices are connected by middleware (OPeLiNK®), and navigation spatial records and time-synchronized data are displayed on the strategy desk. A hyper version of SCOT has currently performed 277 surgeries, including 262 gliomas, 51 awake craniotomies, and 88 photodynamic therapies. For WHO grade 4 glioblastomas, we try to remove contrast-enhanced areas, and for grade 2/3 gliomas, to formulate an extraction strategy for each 3 genotypes, we perform preoperative AI prediction and intraoperative genetic diagnosis for genotype. Intraoperative flow cytometry is useful to predict the genotype (oligodendroglioma) and determine the extent of resection in some cases. Time-synchronized data showed points of surgical maneuvers causing speech arrest in awake surgery and decreases in MEP, and provided feedback during and after surgery. AI technology is also used for preoperative surgical simulation (GRID®), artifact reduction in iMRI, and brain shift prediction. The hyper SCOT supports the optimal removal of gliomas through intraoperative future prognosis prediction through device data and AI analysis. Furthermore, we are developing an AI robot (AIREC) that performs surgery through deep predictive learning, with the aim of commercialization after 2040. This work was partially supported by JST [Moonshot R&amp;D] [Grant Number JPMJMS2031].
INNV-27. LOW/ULTRA-LOW RADIO FREQUENCY MAGNETIC FIELD THERAPIES FOR THE TREATMENT OF CNS TUMORS: RGBM AND DIPG – PAST AND CURRENT RESULTS USING THE EMULATE THERAPEUTICS INC. TECHNOLOGY
Authors: Xavier Figueroa
Journal: Neuro-Oncology (2023)

Abstract EMulate Therapeutics, Inc. (EMTx) has developed a technology that emulates the effects of chemical compounds, via an alternating magnetic field. Our research has led to the development of a radio frequency energy (RFE) signal (A1A) that emulates the effects of paclitaxel. Pre-clinical and animal studies demonstrate an effect in slowing down and inhibiting tumor growth. EMTx has developed a portable medical device that allows for continuous delivery of our A1A signal for up to 14 hours before recharging. The device can be used in combination with current best-supportive-care (BSC) and new investigational treatments. Our technology has been tested in recurrent glioblastoma (rGBM) with very encouraging results in overall survival (OS), especially in combination with BSC. Phase II OS alone was equivalent to BSC (7.2 months BSC OS vs. 7.0 months A1A alone OS) and a considerably improved OS when combined with conventional drug treatment (7.2 months BSC OS versus 10.0 months A1A + BSC OS). EMTx is in the process of seeking humanitarian device exemption (HDE) from the US Food &amp; Drug Administration (FDA) for the Hælo® therapeutic system, our pediatric treatment option. Diffuse intrinsic pontine gliomas (DIPG) are a rare pediatric central nervous system (CNS) tumor. Survival is measured in under 12 months, with no clinical trials demonstrating a significant increase in overall survival in 20 years (9 months median survival post radiation therapy). EMTx’s compassionate use program demonstrated safety and suggested a clinical benefit, with 12 of 14 patients surviving more than 12 months. EMTx is committed to run and complete a pivotal pediatric trial for children diagnosed with DMG/DIPG. The trial will recruit study patients from both the US and India. A total of 35-40 patients will be recruited to participate in this pediatric neuro-oncology trial, which will be a best-supportive-care + single therapy (Hælo®) clinical trial.